RESUMEN
This study was undertaken to investigate the immunoexpression of Bcl-2 family proteins (Bcl-2, Bcl-x, Bax, Bak and Bad) and to evaluate the correlation between the immunoexpression of these proteins and that of cleaved caspase 3, Ki-67 and p53. A tissue microarray (TMA) paraffin block was constructed using gastric carcinoma tissue (test group) and adjacent normal gastric mucosa (control group) from 87 patients who had not previously undergone radiotherapy or chemotherapy. Sections from the TMA block (4 µm) were subjected to immunohistochemistry for Bcl-2, Bcl-x, Bax, Bak, Bad, p53, Ki-67 and cleaved caspase-3. The slides were evaluated by the semi-quantitative method, and the scores obtained (intensity vs. percentage of staining) were correlated with one another and with the apoptotic index, cellular proliferation and data regarding patient survival. The studied proteins were present in the tumor tissue and in the normal gastric mucosa, but at different intensities and with differences in the number of positive cells. There was an association between tumor size and p53 expression, and intestinal type adenocarcinoma was positively correlated with the expression of Bax, Bad and Ki-67. The immunoexpression of Bcl-x, Bak, Bad, p53 and Ki-67 showed statistically significant differences between the tumor tissue and the adjacent normal gastric mucosa. There was an association between the expression of Bax, Bak and Bad in the normal gastric mucosa. No correlation between patient survival and the expression of these proteins was observed. Overexpression of the Bcl-x protein in the adenocarcinomas and the difference in Bcl-x expression between the test and the control group may be related to the anti-apoptotic effect of this protein. The reduced expression of Bak and Bad and the increased expression of p53 and Ki-67 in the adenocarcinomas demonstrate the imbalance between apoptosis and cellular proliferation, which results in uncontrolled tumor cell proliferation.
RESUMEN
EBNA-1 is the only viral protein consistently expressed in all cells latently infected by Epstein-Barr virus (EBV). There is a high frequency of sequence variation within functionally important domains of EBNA-1, with five subtypes identified. Individuals may be infected with multiple EBV strains (classified according to EBNA-1 subtype), but Burkitt's lymphoma (BL) tumours carry a single subtype and exhibit some subtype preference. Subtype variation has also been related to geographical location. In the present study EBNA-1 polymorphisms were examined in a series of haematological malignancies from two distinct geographical regions, Brazil and the United Kingdom. Nucleotide sequence analysis of the carboxy-terminal region of EBNA-1 in 34 cases revealed six distinct sequences, some of which are novel. A new subtype, named V-Ala, was identified. EBNA-1 subtype in tumours differed markedly according to geographical location. In contrast to previous studies, we found evidence of EBNA-1 sequence variation within individual BL tumour samples.